Antenatal prediction of postpartum depression with blood DNA methylation biomarkers.
Antenatal prediction of postpartum depression with blood DNA methylation biomarkers.
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DOI：
10.1038/mp.2013.62
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发表时间：
2014-05
影响因子：
11
通讯作者：
Kaminsky ZA
中科院分区：
文献类型：
--
作者：
Guintivano J;Arad M;Gould TD;Payne JL;Kaminsky ZA
产后抑郁症（PPD）影响了一般人群中约10-18%的妇女，并对母亲和后代造成严重后果。我们假设PPD风险的易感性是由于对雌激素介导的表观遗传变化的敏感性改变，这些表观遗传变化以细胞自主的方式在血液中可检测到。我们研究了雌激素介导的表观遗传重编程事件在海马和PPD的风险，使用跨物种的翻译设计。使用甲基化微阵列在来自怀孕情绪障碍患者的产前血液的前瞻性样本中生成DNA甲基化谱，这些患者产后会和不会发展抑郁症。这些图谱与显示对17β-雌二醇（E2）长期治疗有反应的小鼠海马DNA甲基化变化的同线位置交叉参考。与PPD风险相关的DNA甲基化与E2诱导的DNA甲基化变化显著相关，这表明在PPD风险人群中存在对雌激素为基础的DNA甲基化重编程的敏感性增强。使用合并的小鼠和人类数据，我们在HP 1BP 3和TTC 9 B基因上确定了两个生物标志物基因座，其预测PPD的受试者操作特征（ROC）曲线下面积（曲线下面积（AUC））在产前正常胸腺妇女中为0.87，在产前抑郁妇女的复制样本中为0.12。将血细胞计数数据纳入模型中解释了这种差异，并在抑郁症和正常胸腺妇女中产生了0.96的AUC。通路分析表明，与海马突触可塑性相关的DNA甲基化模式可能是PPD的重要病因。
Postpartum depression (PPD) affects ~10–18% of women in the general population and results in serious consequences to both the mother and offspring. We hypothesized that predisposition to PPD risk is due to an altered sensitivity to estrogen-mediated epigenetic changes that act in a cell autonomous manner detectable in the blood. We investigated estrogen-mediated epigenetic reprogramming events in the hippocampus and risk to PPD using a cross-species translational design. DNA methylation profiles were generated using methylation microarrays in a prospective sample of the blood from the antenatal period of pregnant mood disorder patients who would and would not develop depression postpartum. These profiles were cross-referenced with syntenic locations exhibiting hippocampal DNA methylation changes in the mouse responsive to long-term treatment with 17β-estradiol (E2). DNA methylation associated with PPD risk correlated significantly with E2-induced DNA methylation change, suggesting an enhanced sensitivity to estrogen-based DNA methylation reprogramming exists in those at risk for PPD. Using the combined mouse and human data, we identified two biomarker loci at the HP1BP3 and TTC9B genes that predicted PPD with an area under the receiver operator characteristic (ROC) curve (area under the curve (AUC)) of 0.87 in antenatally euthymic women and 0.12 in a replication sample of antenatally depressed women. Incorporation of blood count data into the model accounted for the discrepancy and produced an AUC of 0.96 across both prepartum depressed and euthymic women. Pathway analyses demonstrated that DNA methylation patterns related to hippocampal synaptic plasticity may be of etiological importance to PPD.
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